Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia
Background Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population. Previous feline PARR studies evaluated clonality of compl...
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| Veröffentlicht in: | Veterinary clinical pathology 2019-10, Vol.48 (S1), p.45-58 |
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| creator | Rout, Emily D. Burnett, Robert C. Yoshimoto, Janna A. Avery, Paul R. Avery, Anne C. |
| description | Background
Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population. Previous feline PARR studies evaluated clonality of complete immunoglobulin heavy chain V‐D‐J (IGH‐VDJ) and T‐cell receptor gamma (TRG) gene rearrangements.
Objectives
We aimed to evaluate the sensitivity and specificity of feline PARR primers targeting complete IGH‐VDJ and TRG rearrangements, as well as incomplete IGH‐DJ, kappa deleting element (Kde), and immunoglobulin lambda light chain (IGL) gene rearrangements in defined feline neoplasms and nonneoplastic controls.
Methods
Fluorescently labeled PCR primers were designed to amplify complete IGH‐VDJ, incomplete IGH‐DJ, Kde, IGL, and TRG gene rearrangements in two multiplexed PCR reactions, and PCR products were analyzed by fragment analysis. Fresh tissue samples from 12 flow cytometrically confirmed B‐cell lymphomas, 26 cytologically confirmed gastric and renal lymphomas of presumed B‐cell origin, 30 flow cytometrically confirmed T‐cell leukemias, and 11 negative control cats were tested.
Results
Using four immunoglobulin primer sets (IGH‐VDJ, IGH‐DJ, Kde, and IGL), clonal immunoglobulin rearrangements were detected in 87% (33/38) of the presumed B‐cell neoplasms. The IGH‐VDJ reaction alone only detected clonality in 50% (19/38) of these cases. TRG rearrangements were clonal in 97% (29/30) of the T‐cell leukemia cases. All negative control samples had polyclonal immunoglobulin and TRG rearrangements.
Conclusions
The PARR assay developed in this study is useful for assessing clonality in feline lymphoid neoplasms. Clonality assessment of incomplete IGH‐DJ, Kde, and IGL rearrangements helped identify clonal B‐cell neoplasms not detected with complete IGH‐VDJ PARR alone. |
| doi_str_mv | 10.1111/vcp.12767 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2283977249</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2283977249</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3537-badf449ebace60da37d1922e4a0174072780aaee7dd4e4118a68bb64b0d7055c3</originalsourceid><addsrcrecordid>eNp1kc1O3DAURq2Kqkwpi75AZYkNlRrwX-JkiUZtqYRUFlCxixz7ZmLk2GmcUGXHI7Dv2_VJ8HSgC6R6Y8n3-Phefwi9p-SEpnV6p4cTymQhX6EVrXiV0SK_2UMrwmSeFbxk--htjLeE8DwdvUH7nApZMkZW6PdZjBBjD37CocW272cfNi40s7Med6DuFqw7Zf2nlzVnN930XFPe4Ks_9w8anMMjaBimMGLtglfOTgueIE7Wb3C6N3WAjVUbH6KN2zdbSDrAbumHLliDPYTBqWjVO_S6VS7C4dN-gK6_fL5an2cX379-W59dZJrnXGaNMq0QFTRKQ0GM4tLQijEQilApiGSyJEoBSGMECEpLVZRNU4iGGEnyXPMDdLzzDmP4OadO697G7SQqtTLHmrGSV1IyUSX06AV6G-YxDZkonr5X8ormifq4o_QYYhyhrYfR9mpcakrqbWJ1Sqz-m1hiPzwZ56YH8498jigBpzvgl3Ww_N9U_1hf7pSP2HOkEQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2303573915</pqid></control><display><type>article</type><title>Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Rout, Emily D. ; Burnett, Robert C. ; Yoshimoto, Janna A. ; Avery, Paul R. ; Avery, Anne C.</creator><creatorcontrib>Rout, Emily D. ; Burnett, Robert C. ; Yoshimoto, Janna A. ; Avery, Paul R. ; Avery, Anne C.</creatorcontrib><description>Background
Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population. Previous feline PARR studies evaluated clonality of complete immunoglobulin heavy chain V‐D‐J (IGH‐VDJ) and T‐cell receptor gamma (TRG) gene rearrangements.
Objectives
We aimed to evaluate the sensitivity and specificity of feline PARR primers targeting complete IGH‐VDJ and TRG rearrangements, as well as incomplete IGH‐DJ, kappa deleting element (Kde), and immunoglobulin lambda light chain (IGL) gene rearrangements in defined feline neoplasms and nonneoplastic controls.
Methods
Fluorescently labeled PCR primers were designed to amplify complete IGH‐VDJ, incomplete IGH‐DJ, Kde, IGL, and TRG gene rearrangements in two multiplexed PCR reactions, and PCR products were analyzed by fragment analysis. Fresh tissue samples from 12 flow cytometrically confirmed B‐cell lymphomas, 26 cytologically confirmed gastric and renal lymphomas of presumed B‐cell origin, 30 flow cytometrically confirmed T‐cell leukemias, and 11 negative control cats were tested.
Results
Using four immunoglobulin primer sets (IGH‐VDJ, IGH‐DJ, Kde, and IGL), clonal immunoglobulin rearrangements were detected in 87% (33/38) of the presumed B‐cell neoplasms. The IGH‐VDJ reaction alone only detected clonality in 50% (19/38) of these cases. TRG rearrangements were clonal in 97% (29/30) of the T‐cell leukemia cases. All negative control samples had polyclonal immunoglobulin and TRG rearrangements.
Conclusions
The PARR assay developed in this study is useful for assessing clonality in feline lymphoid neoplasms. Clonality assessment of incomplete IGH‐DJ, Kde, and IGL rearrangements helped identify clonal B‐cell neoplasms not detected with complete IGH‐VDJ PARR alone.</description><identifier>ISSN: 0275-6382</identifier><identifier>EISSN: 1939-165X</identifier><identifier>DOI: 10.1111/vcp.12767</identifier><identifier>PMID: 31478220</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; antigen receptor rearrangement ; Cat Diseases - diagnosis ; Cat Diseases - genetics ; Cat Diseases - pathology ; Cats ; Diagnostic software ; Female ; Gene Rearrangement ; Heavy chains ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Light Chains - genetics ; Immunoglobulins ; Leukemia ; Leukemia, Lymphoid - diagnosis ; Leukemia, Lymphoid - genetics ; Leukemia, Lymphoid - pathology ; Leukemia, Lymphoid - veterinary ; Lymphocytes - pathology ; Lymphoma ; Male ; Population studies ; Primers ; Receptors, Antigen - genetics ; Sensitivity and Specificity ; Tissue analysis ; Tumors ; T‐cell receptor gamma</subject><ispartof>Veterinary clinical pathology, 2019-10, Vol.48 (S1), p.45-58</ispartof><rights>2019 American Society for Veterinary Clinical Pathology</rights><rights>2019 American Society for Veterinary Clinical Pathology.</rights><rights>Copyright © 2019 American Society for Veterinary Clinical Pathology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3537-badf449ebace60da37d1922e4a0174072780aaee7dd4e4118a68bb64b0d7055c3</citedby><cites>FETCH-LOGICAL-c3537-badf449ebace60da37d1922e4a0174072780aaee7dd4e4118a68bb64b0d7055c3</cites><orcidid>0000-0003-1435-8532</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fvcp.12767$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fvcp.12767$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31478220$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rout, Emily D.</creatorcontrib><creatorcontrib>Burnett, Robert C.</creatorcontrib><creatorcontrib>Yoshimoto, Janna A.</creatorcontrib><creatorcontrib>Avery, Paul R.</creatorcontrib><creatorcontrib>Avery, Anne C.</creatorcontrib><title>Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia</title><title>Veterinary clinical pathology</title><addtitle>Vet Clin Pathol</addtitle><description>Background
Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population. Previous feline PARR studies evaluated clonality of complete immunoglobulin heavy chain V‐D‐J (IGH‐VDJ) and T‐cell receptor gamma (TRG) gene rearrangements.
Objectives
We aimed to evaluate the sensitivity and specificity of feline PARR primers targeting complete IGH‐VDJ and TRG rearrangements, as well as incomplete IGH‐DJ, kappa deleting element (Kde), and immunoglobulin lambda light chain (IGL) gene rearrangements in defined feline neoplasms and nonneoplastic controls.
Methods
Fluorescently labeled PCR primers were designed to amplify complete IGH‐VDJ, incomplete IGH‐DJ, Kde, IGL, and TRG gene rearrangements in two multiplexed PCR reactions, and PCR products were analyzed by fragment analysis. Fresh tissue samples from 12 flow cytometrically confirmed B‐cell lymphomas, 26 cytologically confirmed gastric and renal lymphomas of presumed B‐cell origin, 30 flow cytometrically confirmed T‐cell leukemias, and 11 negative control cats were tested.
Results
Using four immunoglobulin primer sets (IGH‐VDJ, IGH‐DJ, Kde, and IGL), clonal immunoglobulin rearrangements were detected in 87% (33/38) of the presumed B‐cell neoplasms. The IGH‐VDJ reaction alone only detected clonality in 50% (19/38) of these cases. TRG rearrangements were clonal in 97% (29/30) of the T‐cell leukemia cases. All negative control samples had polyclonal immunoglobulin and TRG rearrangements.
Conclusions
The PARR assay developed in this study is useful for assessing clonality in feline lymphoid neoplasms. Clonality assessment of incomplete IGH‐DJ, Kde, and IGL rearrangements helped identify clonal B‐cell neoplasms not detected with complete IGH‐VDJ PARR alone.</description><subject>Animals</subject><subject>antigen receptor rearrangement</subject><subject>Cat Diseases - diagnosis</subject><subject>Cat Diseases - genetics</subject><subject>Cat Diseases - pathology</subject><subject>Cats</subject><subject>Diagnostic software</subject><subject>Female</subject><subject>Gene Rearrangement</subject><subject>Heavy chains</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Light Chains - genetics</subject><subject>Immunoglobulins</subject><subject>Leukemia</subject><subject>Leukemia, Lymphoid - diagnosis</subject><subject>Leukemia, Lymphoid - genetics</subject><subject>Leukemia, Lymphoid - pathology</subject><subject>Leukemia, Lymphoid - veterinary</subject><subject>Lymphocytes - pathology</subject><subject>Lymphoma</subject><subject>Male</subject><subject>Population studies</subject><subject>Primers</subject><subject>Receptors, Antigen - genetics</subject><subject>Sensitivity and Specificity</subject><subject>Tissue analysis</subject><subject>Tumors</subject><subject>T‐cell receptor gamma</subject><issn>0275-6382</issn><issn>1939-165X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O3DAURq2Kqkwpi75AZYkNlRrwX-JkiUZtqYRUFlCxixz7ZmLk2GmcUGXHI7Dv2_VJ8HSgC6R6Y8n3-Phefwi9p-SEpnV6p4cTymQhX6EVrXiV0SK_2UMrwmSeFbxk--htjLeE8DwdvUH7nApZMkZW6PdZjBBjD37CocW272cfNi40s7Med6DuFqw7Zf2nlzVnN930XFPe4Ks_9w8anMMjaBimMGLtglfOTgueIE7Wb3C6N3WAjVUbH6KN2zdbSDrAbumHLliDPYTBqWjVO_S6VS7C4dN-gK6_fL5an2cX379-W59dZJrnXGaNMq0QFTRKQ0GM4tLQijEQilApiGSyJEoBSGMECEpLVZRNU4iGGEnyXPMDdLzzDmP4OadO697G7SQqtTLHmrGSV1IyUSX06AV6G-YxDZkonr5X8ormifq4o_QYYhyhrYfR9mpcakrqbWJ1Sqz-m1hiPzwZ56YH8498jigBpzvgl3Ww_N9U_1hf7pSP2HOkEQ</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Rout, Emily D.</creator><creator>Burnett, Robert C.</creator><creator>Yoshimoto, Janna A.</creator><creator>Avery, Paul R.</creator><creator>Avery, Anne C.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1435-8532</orcidid></search><sort><creationdate>201910</creationdate><title>Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia</title><author>Rout, Emily D. ; Burnett, Robert C. ; Yoshimoto, Janna A. ; Avery, Paul R. ; Avery, Anne C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3537-badf449ebace60da37d1922e4a0174072780aaee7dd4e4118a68bb64b0d7055c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>antigen receptor rearrangement</topic><topic>Cat Diseases - diagnosis</topic><topic>Cat Diseases - genetics</topic><topic>Cat Diseases - pathology</topic><topic>Cats</topic><topic>Diagnostic software</topic><topic>Female</topic><topic>Gene Rearrangement</topic><topic>Heavy chains</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Light Chains - genetics</topic><topic>Immunoglobulins</topic><topic>Leukemia</topic><topic>Leukemia, Lymphoid - diagnosis</topic><topic>Leukemia, Lymphoid - genetics</topic><topic>Leukemia, Lymphoid - pathology</topic><topic>Leukemia, Lymphoid - veterinary</topic><topic>Lymphocytes - pathology</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Population studies</topic><topic>Primers</topic><topic>Receptors, Antigen - genetics</topic><topic>Sensitivity and Specificity</topic><topic>Tissue analysis</topic><topic>Tumors</topic><topic>T‐cell receptor gamma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rout, Emily D.</creatorcontrib><creatorcontrib>Burnett, Robert C.</creatorcontrib><creatorcontrib>Yoshimoto, Janna A.</creatorcontrib><creatorcontrib>Avery, Paul R.</creatorcontrib><creatorcontrib>Avery, Anne C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Veterinary clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rout, Emily D.</au><au>Burnett, Robert C.</au><au>Yoshimoto, Janna A.</au><au>Avery, Paul R.</au><au>Avery, Anne C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia</atitle><jtitle>Veterinary clinical pathology</jtitle><addtitle>Vet Clin Pathol</addtitle><date>2019-10</date><risdate>2019</risdate><volume>48</volume><issue>S1</issue><spage>45</spage><epage>58</epage><pages>45-58</pages><issn>0275-6382</issn><eissn>1939-165X</eissn><abstract>Background
Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population. Previous feline PARR studies evaluated clonality of complete immunoglobulin heavy chain V‐D‐J (IGH‐VDJ) and T‐cell receptor gamma (TRG) gene rearrangements.
Objectives
We aimed to evaluate the sensitivity and specificity of feline PARR primers targeting complete IGH‐VDJ and TRG rearrangements, as well as incomplete IGH‐DJ, kappa deleting element (Kde), and immunoglobulin lambda light chain (IGL) gene rearrangements in defined feline neoplasms and nonneoplastic controls.
Methods
Fluorescently labeled PCR primers were designed to amplify complete IGH‐VDJ, incomplete IGH‐DJ, Kde, IGL, and TRG gene rearrangements in two multiplexed PCR reactions, and PCR products were analyzed by fragment analysis. Fresh tissue samples from 12 flow cytometrically confirmed B‐cell lymphomas, 26 cytologically confirmed gastric and renal lymphomas of presumed B‐cell origin, 30 flow cytometrically confirmed T‐cell leukemias, and 11 negative control cats were tested.
Results
Using four immunoglobulin primer sets (IGH‐VDJ, IGH‐DJ, Kde, and IGL), clonal immunoglobulin rearrangements were detected in 87% (33/38) of the presumed B‐cell neoplasms. The IGH‐VDJ reaction alone only detected clonality in 50% (19/38) of these cases. TRG rearrangements were clonal in 97% (29/30) of the T‐cell leukemia cases. All negative control samples had polyclonal immunoglobulin and TRG rearrangements.
Conclusions
The PARR assay developed in this study is useful for assessing clonality in feline lymphoid neoplasms. Clonality assessment of incomplete IGH‐DJ, Kde, and IGL rearrangements helped identify clonal B‐cell neoplasms not detected with complete IGH‐VDJ PARR alone.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31478220</pmid><doi>10.1111/vcp.12767</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1435-8532</orcidid></addata></record> |
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| ispartof | Veterinary clinical pathology, 2019-10, Vol.48 (S1), p.45-58 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals antigen receptor rearrangement Cat Diseases - diagnosis Cat Diseases - genetics Cat Diseases - pathology Cats Diagnostic software Female Gene Rearrangement Heavy chains Immunoglobulin Heavy Chains - genetics Immunoglobulin Light Chains - genetics Immunoglobulins Leukemia Leukemia, Lymphoid - diagnosis Leukemia, Lymphoid - genetics Leukemia, Lymphoid - pathology Leukemia, Lymphoid - veterinary Lymphocytes - pathology Lymphoma Male Population studies Primers Receptors, Antigen - genetics Sensitivity and Specificity Tissue analysis Tumors T‐cell receptor gamma |
| title | Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia |
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